The Association between Blood Test Trends and Undiagnosed Cancer: A Systematic Review and Critical Appraisal.

Clinical guidelines include monitoring blood test abnormalities to identify patients at increased risk of undiagnosed cancer. Noting blood test changes over time may improve cancer risk stratification by considering a patient's individual baseline and important changes within the normal range. We aimed to review the published literature to understand the association between blood test trends and undiagnosed cancer. MEDLINE and EMBASE were searched until 15 May 2023 for studies assessing the association between blood test trends and undiagnosed cancer. We used descriptive summaries and narratively synthesised studies. We included 29 articles. Common blood tests were haemoglobin (24%, n = 7), C-reactive protein (17%, n = 5), and fasting blood glucose (17%, n = 5), and common cancers were pancreatic (29%, n = 8) and colorectal (17%, n = 5). Of the 30 blood tests studied, an increasing trend in eight (27%) was associated with eight cancer types, and a decreasing trend in 17 (57%) with 10 cancer types. No association was reported between trends in 11 (37%) tests and breast, bile duct, glioma, haematological combined, liver, prostate, or thyroid cancers. Our review highlights trends in blood tests that could facilitate the identification of individuals at increased risk of undiagnosed cancer. For most possible combinations of tests and cancers, there was limited or no evidence.

Adequacy of clinical guideline recommendations for patients with low-risk cancer managed with monitoring: systematic review.

OBJECTIVES: The aim of this systematic review was to summarize national and international guidelines that made recommendations for monitoring patients diagnosed with low-risk cancer. It appraised the quality of guidelines and determined whether the guidelines adequately identified patients for monitoring, specified which tests to use, defined monitoring intervals, and stated triggers for further intervention. It then assessed the evidence to support each recommendation. STUDY DESIGN AND SETTING: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses, we searched PubMed and Turning Research into Practice databases for national and international guidelines' that were written in English and developed or updated between 2012 and 2023. Quality of individual guidelines was assessed using the AGREE II tool. RESULTS: Across the 41 published guidelines, 48 different recommendations were identified: 15 (31%) for prostate cancer, 11 (23%) for renal cancer, 6 (12.5%) for thyroid cancer, and 10 (21%) for blood cancer. The remaining 6 (12.5%) were for brain, gastrointestinal, oral cavity, bone and pheochromocytoma and paraganglioma cancer. When combining all guidelines, 48 (100%) stated which patients qualify for monitoring, 31 (65%) specified which tests to use, 25 (52%) provided recommendations for surveillance intervals, and 23 (48%) outlined triggers to initiate intervention. Across all cancer sites, there was a strong positive trend with higher levels of evidence being associated with an increased likelihood of a recommendation being specific (P = 0.001) and the evidence for intervals was based on expert opinion or other guidance. CONCLUSION: With the exception of prostate cancer, the evidence base for monitoring low-risk cancer is weak and consequently recommendations in clinical guidelines are inconsistent. There is a lack of direct evidence to support monitoring recommendations in the literature making guideline developers reliant on expert opinion, alternative guidelines, or indirect or nonspecific evidence.

The Accuracy of Computed Tomography Angiography Compared With Technetium-99m Labelled Red Blood Cell Scintigraphy for the Diagnosis and Localization of Acute Gastrointestinal Bleeding: A Systematic Review and Meta-Analysis.

Imaging tests are commonly used as an initial or early investigation for patients presenting with suspected acute gastrointestinal bleeding (AGIB). However, controversy remains regarding which of two frequently used modalities, computed tomography angiography (CTA) or technetium-99m labelled red blood cell scintigraphy (RBCS), is most accurate. This systematic review and meta-analysis was performed to compare the accuracy of CTA and RBCS for the detection and localization of AGIB. Five electronic databases were searched with additional manual searching of reference lists of relevant publications identified during the search. Two reviewers independently performed screening, data extraction and methodological assessments. Where appropriate, the bivariate model was used for meta-analysis of sensitivities and specificities for the detection of bleeding and Freeman-Tukey double-arcsine transformation used for meta-analysis of proportions of correctly localized bleeding sites. Forty-four unique primary studies were included: twenty-two investigating CTA, seventeen investigating RBCS and five investigating both modalities. Meta-analysis produced similar pooled sensitivities; 0.83 (95% CI 0.74-0.90) and 0.84 (0.68-0.92) for CTA and RBCS respectively. Pooled specificity for CTA was higher than RBCS; 0.90 (0.72-0.97) and 0.84 (0.71-0.91) respectively. However, differences were not statistically significant. CTA was superior to RBCS in correctly localizing bleeding; pooled proportions of 1.00 (0.98-1.00) and 0.90 (0.83-0.96) respectively (statistically significant difference, P < 0.001). There is no evidence that CTA and RBCS have different diagnostic performance with respect to the detection of AGIB. However, CTA is superior to RBCS in terms of correctly localising the bleeding site, supporting usage of CTA over RBCS as the first line imaging investigation.

Deceptive measures of progress in the NHS long-term plan for cancer: case-based vs. population-based measures.

The NHS Long Term Plan for cancer aims to increase early-stage diagnoses from 50% to 75% and to have 55,000 more people each year survive their cancer for at least 5 years following diagnosis. The targets measures are flawed and could be met without improving outcomes that really matter to patients. The proportion of early-stage diagnoses could increase, while the number of patients presenting at a late-stage remains the same. More patients could survive their cancer for longer, but lead time and overdiagnosis bias make it impossible to know whether anyone had their life prolonged. The target measures should switch from biased case-based measures to unbiased population-based measures that reflect the key objectives in cancer care: reducing late-stage incidence and mortality.

Long-Term Effect of Weight Regain Following Behavioral Weight Management Programs on Cardiometabolic Disease Incidence and Risk: Systematic Review and Meta-Analysis.

BACKGROUND: Behavioral weight management programs (BWMPs) enhance weight loss in the short term, but longer term cardiometabolic effects are uncertain as weight is commonly regained. We assessed the impact of weight regain after BWMPs on cardiovascular risk factors, diabetes, and cardiovascular disease. METHODS: Trial registries, 11 databases, and forward-citation searching (latest search, December 19) were used to identify articles published in English, from any geographical region. Randomized trials of BWMPs in adults with overweight/obesity reporting cardiometabolic outcomes at ≥12 months at and after program end were included. Differences between more intensive interventions and comparator groups were synthesized using mixed-effects, meta-regression, and time-to-event models to assess the impact of weight regain on cardiovascular disease incidence and risk. RESULTS: One hundred twenty-four trials reporting on ≥1 cardiometabolic outcomes with a median follow-up of 28 (range, 11-360) months after program end were included. Median baseline participant body mass index was 33 kg/m2; median age was 51 years. Eight and 15 study arms (7889 and 4202 participants, respectively) examined the incidence of cardiovascular disease and type 2 diabetes, respectively, with imprecise evidence of a lower incidence for at least 5 years. Weight regain in BWMPs relative to comparators reduced these differences. One and 5 years after program end, total cholesterol/HDL (high-density lipoprotein) ratio was 1.5 points lower at both times (82 studies; 19 003 participants), systolic blood pressure was 1.5 mm mercury and 0.4 mm lower (84 studies; 30 836 participants), and HbA1c (%) 0.38 lower at both times (94 studies; 28 083 participants). Of the included studies, 22% were judged at high risk of bias; removing these did not meaningfully change results. CONCLUSIONS: Despite weight regain, BWMPs reduce cardiometabolic risk factors with effects lasting at least 5 years after program end and dwindling with weight regain. Evidence that they reduce the incidence of cardiovascular disease or diabetes is less certain. Few studies followed participants for ≥5 years. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42018105744.

Weight regain and mental health outcomes following behavioural weight management programmes: A systematic review with meta-analyses.

Behavioural weight management programmes (BWMPs) lead to weight loss but subsequent weight regain may harm mental health outcomes. We searched for randomised trials of BWMPs in adults with overweight/obesity with follow-up ≥12 months from baseline that measured weight change both at and after programme-end. We included only studies reporting mental health at or after programme-end. We meta-analysed changes in various mental health outcomes using a random-effects model by nature of the comparator group and by time since programme end. Subgroup analysis explored heterogeneity. We used mixed models and meta-regression to analyse the association between change in weight and change in depression and/or anxiety over time, with higher scores indicating greater depression and/or anxiety. We included 47 studies. When comparing BWMPs (diet and/or exercise) to control, most estimates included the possibility of no difference, but pooled estimates for psychological wellbeing, self-esteem and mental-health composite scores at programme-end, anxiety at 1-6 months, and depression at 7-12 months after programme-end suggested improvements in intervention arms relative to control, with 95% CIs excluding no difference. Pooled estimates found no evidence that BWMPs harmed mental health at programme end or beyond. Mental health composite scores at programme-end favoured diet and exercise interventions over diet alone, with 95% CIs excluding no difference. All other measures and timepoints included the possibility of no difference or could not be meta-analysed due to high heterogeneity or a paucity of data. Mixed models and meta-regression of the association between change in depression and/or anxiety scores over time, and change in weight, were inconclusive. Despite weight regain after BWMPs, our meta-analyses found no evidence of mental health harm and some evidence that BWMPs may improve some dimensions of mental health at and after programme-end.

Weight regain after behavioural weight management programmes and its impact on quality of life and cost effectiveness: Evidence synthesis and health economic analyses.

AIMS: We used data from a recent systematic review to investigate weight regain after behavioural weight management programmes (BWMPs, sometimes referred to as lifestyle modification programmes) and its impact on quality-of-life and cost-effectiveness. MATERIALS AND METHODS: Trial registries, databases and forward-citation searching (latest search December 2019) were used to identify randomized trials of BWMPs in adults with overweight/obesity reporting outcomes at ≥12 months, and after programme end. Two independent reviewers screened records. One reviewer extracted data and a second checked them. The differences between intervention and control groups were synthesized using mixed-effect, meta-regression and time-to-event models. We examined associations between weight difference and difference in quality-of-life. Cost-effectiveness was estimated from a health sector perspective. RESULTS: In total, 155 trials (n > 150 000) contributed to analyses. The longest follow-up was 23 years post-programme. At programme end, intervention groups achieved -2.8 kg (95%CI -3.2 to -2.4) greater weight loss than controls. Weight regain after programme end was 0.12-0.32 kg/year greater in intervention relative to control groups, with a between-group difference evident for at least 5 years. Quality-of-life increased in intervention groups relative to control at programme end and thereafter returned to control as the difference in weight between groups diminished. BWMPs with this initial weight loss and subsequent regain would be cost-effective if delivered for under £560 (£8.80-£3900) per person. CONCLUSIONS: Modest rates of weight regain, with persistent benefits for several years, should encourage health care practitioners and policymakers to offer obesity treatments that cost less than our suggested thresholds as a cost-effective intervention to improve long-term weight management. REGISTRATION: The review is registered on PROSPERO, CRD42018105744.

Artificial Intelligence Tool for Assessment of Indeterminate Pulmonary Nodules Detected with CT.

Background Limited data are available regarding whether computer-aided diagnosis (CAD) improves assessment of malignancy risk in indeterminate pulmonary nodules (IPNs). Purpose To evaluate the effect of an artificial intelligence-based CAD tool on clinician IPN diagnostic performance and agreement for both malignancy risk categories and management recommendations. Materials and Methods This was a retrospective multireader multicase study performed in June and July 2020 on chest CT studies of IPNs. Readers used only CT imaging data and provided an estimate of malignancy risk and a management recommendation for each case without and with CAD. The effect of CAD on average reader diagnostic performance was assessed using the Obuchowski-Rockette and Dorfman-Berbaum-Metz method to calculate estimates of area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Multirater Fleiss κ statistics were used to measure interobserver agreement for malignancy risk and management recommendations. Results A total of 300 chest CT scans of IPNs with maximal diameters of 5-30 mm (50.0% malignant) were reviewed by 12 readers (six radiologists, six pulmonologists) (patient median age, 65 years; IQR, 59-71 years; 164 [55%] men). Readers' average AUC improved from 0.82 to 0.89 with CAD (P < .001). At malignancy risk thresholds of 5% and 65%, use of CAD improved average sensitivity from 94.1% to 97.9% (P = .01) and from 52.6% to 63.1% (P < .001), respectively. Average reader specificity improved from 37.4% to 42.3% (P = .03) and from 87.3% to 89.9% (P = .05), respectively. Reader interobserver agreement improved with CAD for both the less than 5% (Fleiss κ, 0.50 vs 0.71; P < .001) and more than 65% (Fleiss κ, 0.54 vs 0.71; P < .001) malignancy risk categories. Overall reader interobserver agreement for management recommendation categories (no action, CT surveillance, diagnostic procedure) also improved with CAD (Fleiss κ, 0.44 vs 0.52; P = .001). Conclusion Use of computer-aided diagnosis improved estimation of indeterminate pulmonary nodule malignancy risk on chest CT scans and improved interobserver agreement for both risk stratification and management recommendations. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Yanagawa in this issue.

Oxford consensus on primary cam morphology and femoroacetabular impingement syndrome: part 1-definitions, terminology, taxonomy and imaging outcomes.

INTRODUCTION: Primary cam morphology is a mostly benign bony prominence that develops at the femoral head-neck junction of the hip, but it is highly prevalent in many athlete populations. In the small proportion of athletes for whom it is not benign, the resulting hip osteoarthritis can be debilitating. Clinicians, athletes, patients and researchers do not yet agree on important primary cam morphology elements. We aimed to ascertain and improve the level of agreement on primary cam morphology definitions, terminology, taxonomy and imaging outcome measures. METHODS: To collect and aggregate informed opinions, an expert panel-the Young Athlete's Hip Research Collaborative-rated primary cam morphology definition, terminology, taxonomy and imaging outcome statements through an online Delphi exercise followed by an online meeting to explore areas of tension and dissent. Reporting followed Conducting and REporting DElphi Studies. RESULTS: A diverse and inclusive Delphi panel (n=65 for rounds 1 and 2, representing 18 countries; 6 stakeholder groups; 40% women) agreed on 35 of 47 statements in 4 domains, while surfacing areas of tension and dissent. This Delphi panel agreed on four key issues essential to moving research and clinical care forward around primary cam morphology. They agreed on: (1) definition, confirming its conceptual attributes (tissue type, size, location, shape and ownership); (2) terminology-use 'morphology' and not terms with a negative connotation like 'lesion', 'abnormality' or 'deformity'; (3) taxonomy, distinguishing between primary and secondary cam morphology, and (4) imaging outcomes, a continuous bone/cartilage alpha angle on radial femoral head-neck MRI for primary cam morphology aetiology research. CONCLUSION: This consensus provides athletes, patients, clinicians and researchers with a strong foundation to guide more precise communication, better clinical decision-making and higher value research about primary cam morphology and its natural history.

Oxford consensus on primary cam morphology and femoroacetabular impingement syndrome: part 2-research priorities on conditions affecting the young person's hip.

INTRODUCTION: Primary cam morphology is highly prevalent in many athlete populations, causing debilitating hip osteoarthritis in some. Existing research is mired in confusion partly because stakeholders have not agreed on key primary cam morphology elements or a prioritised research agenda. We aimed to inform a more rigorous, inclusive and evidence-based approach to research on primary cam morphology and its natural history by working towards agreement on a set of research priorities for conditions affecting the young person's hip. METHODS: An international expert panel-the Young Athlete's Hip Research (YAHiR) Collaborative-rated research priority statements through an online two-round Delphi exercise and met online to explore areas of tension and dissent. Panellists ranked the prioritised research statements according to the Essential National Health Research (ENHR) ranking strategy. Reporting of results followed REPRISE (REporting guideline for PRIority SEtting of health). RESULTS: A diverse Delphi panel (n=65, Delphi rounds 1 and 2; three ENHR strategy surveys: n=49; n=44; n=42) from 18 countries representing six stakeholder groups, prioritised and ranked 18 of 38 research priority statements. The prioritised statements outlined seven research domains: (1) best practice physiotherapy, (2) rehabilitation progression and return to sport, (3) exercise intervention and load management, (4) primary cam morphology prognosis and aetiology, (5) femoroacetabular impingement syndrome prognosis and aetiology, (6) diagnostic criteria, and (7) screening. The panel recommended areas of tension and dissent for the research community to focus on immediately. CONCLUSION: While informing more rigorous, inclusive and evidence-based research, this consensus is a roadmap for researchers, policy-makers and funders to implement research dedicated to reducing the cost and burden of hip disease related to primary cam morphology.

Association between characteristics of behavioural weight loss programmes and weight change after programme end: systematic review and meta-analysis.

OBJECTIVE: To determine if the characteristics of behavioural weight loss programmes influence the rate of change in weight after the end of the programme. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Trial registries, 11 electronic databases, and forward citation searching (from database inception; latest search December 2019). Randomised trials of behavioural weight loss programmes in adults with overweight or obesity, reporting outcomes at ≥12 months, including at the end of the programme and after the end of the programme. REVIEW METHODS: Studies were screened by two independent reviewers with discrepancies resolved by discussion. 5% of the studies identified in the searches met the inclusion criteria. One reviewer extracted the data and a second reviewer checked the data. Risk of bias was assessed with Cochrane's risk of bias tool (version 1). The rate of change in weight was calculated (kg/month; converted to kg/year for interpretability) after the end of the programme in the intervention versus control groups by a mixed model with a random intercept. Associations between the rate of change in weight and prespecified variables were tested. RESULTS: Data were analysed from 249 trials (n=59 081) with a mean length of follow-up of two years (longest 30 years). 56% of studies (n=140) had an unclear risk of bias, 21% (n=52) a low risk, and 23% (n=57) a high risk of bias. Regain in weight was faster in the intervention versus the no intervention control groups (0.12-0.32 kg/year) but the difference between groups was maintained for at least five years. Each kilogram of weight lost at the end of the programme was associated with faster regain in weight at a rate of 0.13-0.19 kg/year. Financial incentives for weight loss were associated with faster regain in weight at a rate of 1-1.5 kg/year. Compared with programmes with no meal replacements, interventions involving partial meal replacements were associated with faster regain in weight but not after adjustment for weight loss during the programme. Access to the programme outside of the study was associated with slower regain in weight. Programmes where the intensity of the interaction reduced gradually were also associated with slower regain in weight in the multivariable analysis, although the point estimate suggested that the association was small. Other characteristics did not explain the heterogeneity in regain in weight. CONCLUSION: Faster regain in weight after weight loss was associated with greater initial weight loss, but greater initial weight loss was still associated with reduced weight for at least five years after the end of the programme, after which data were limited. Continued availability of the programme to participants outside of the study predicted a slower regain in weight, and provision of financial incentives predicted faster regain in weight; no other clear associations were found. STUDY REGISTRATION: PROSPERO CRD42018105744.

Primary cam morphology; bump, burden or bog-standard? A concept analysis.

BACKGROUND: Cam morphology, a distinct bony morphology of the hip, is prevalent in many athletes, and a risk factor for hip-related pain and osteoarthritis. Secondary cam morphology, due to existing or previous hip disease (eg, Legg-Calve-Perthes disease), is well-described. Cam morphology not clearly associated with a disease is a challenging concept for clinicians, scientists and patients. We propose this morphology, which likely develops during skeletal maturation as a physiological response to load, should be referred to as primary cam morphology. The aim of this study was to introduce and clarify the concept of primary cam morphology. DESIGN: We conducted a concept analysis of primary cam morphology using articles that reported risk factors associated with primary cam morphology; we excluded articles on secondary cam morphology. The concept analysis method is a rigorous eight-step process designed to clarify complex 'concepts'; the end product is a precise definition that supports the theoretical basis of the chosen concept. RESULTS: We propose five defining attributes of primary cam morphology-tissue type, size, site, shape and ownership-in a new conceptual and operational definition. Primary cam morphology is a cartilage or bony prominence (bump) of varying size at the femoral head-neck junction, which changes the shape of the femoral head from spherical to aspherical. It often occurs in asymptomatic male athletes in both hips. The cartilage or bone alpha angle (calculated from radiographs, CT or MRI) is the most common method to measure cam morphology. We found inconsistent reporting of primary cam morphology taxonomy, terminology, and how the morphology is operationalised. CONCLUSION: We introduce and clarify primary cam morphology, and propose a new conceptual and operational definition. Several elements of the concept of primary cam morphology remain unclear and contested. Experts need to agree on the new taxonomy, terminology and definition that better reflect the primary cam morphology landscape-a bog-standard bump in most athletic hips, and a possible hip disease burden in a selected few.

Clinical prediction tools to identify patients at highest risk of myeloma in primary care: a retrospective open cohort study.

BACKGROUND: Patients with myeloma experience substantial delays in their diagnosis, which can adversely affect their prognosis. AIM: To generate a clinical prediction rule to identify primary care patients who are at highest risk of myeloma. DESIGN AND SETTING: Retrospective open cohort study using electronic health records data from the UK's Clinical Practice Research Datalink (CPRD) between 1 January 2000 and 1 January 2014. METHOD: Patients from the CPRD were included in the study if they were aged ≥40 years, had two full blood counts within a year, and had no previous diagnosis of myeloma. Cases of myeloma were identified in the following 2 years. Derivation and external validation datasets were created based on geographical region. Prediction equations were estimated using Cox proportional hazards models including patient characteristics, symptoms, and blood test results. Calibration, discrimination, and clinical utility were evaluated in the validation set. RESULTS: Of 1 281 926 eligible patients, 737 (0.06%) were diagnosed with myeloma within 2 years. Independent predictors of myeloma included: older age; male sex; back, chest and rib pain; nosebleeds; low haemoglobin, platelets, and white cell count; and raised mean corpuscular volume, calcium, and erythrocyte sedimentation rate. A model including symptoms and full blood count had an area under the curve of 0.84 (95% CI = 0.81 to 0.87) and sensitivity of 62% (95% CI = 55% to 68%) at the highest risk decile. The corresponding statistics for a second model, which also included calcium and inflammatory markers, were an area under the curve of 0.87 (95% CI = 0.84 to 0.90) and sensitivity of 72% (95% CI = 66% to 78%). CONCLUSION: The implementation of these prediction rules would highlight the possibility of myeloma in patients where GPs do not suspect myeloma. Future research should focus on the prospective evaluation of further external validity and the impact on clinical practice.

Faecal immunochemical testing for adults with symptoms of colorectal cancer attending English primary care: a retrospective cohort study of 14 487 consecutive test requests.

BACKGROUND: Faecal immunochemical testing (FIT) is recommended by the National Institute for Health and Care Excellence (NICE) to triage symptomatic primary care patients for further investigation of colorectal cancer. AIM: To ascertain the diagnostic performance of FIT in symptomatic adult primary care patients. METHODS: Faecal samples from routine primary care practice in Oxfordshire, UK were analysed using the HM-JACKarc FIT method between March 2017 and March 2020. Clinical details were recorded. Patients were followed for up to 36 months in linked hospital records for evidence of benign and serious (colorectal cancer, high-risk adenomas and bowel inflammation) colorectal disease. The diagnostic accuracy of FIT is reported by gender, age group and FIT threshold. RESULTS: In 9896 adult patients with at least 6-month follow-up, a FIT result ≥10 µg Hb/g faeces had a sensitivity for colorectal cancer of 90.5% (95% CI 84.9%-96.1%), specificity 91.3% (90.8%-91.9%), positive predictive value (PPV) 10.1% (8.15%-12.0%) and negative predictive value (NPV) 99.9% (99.8%-100.0%). The PPV and specificity for serious colorectal disease were higher and the sensitivity and NPV lower than for colorectal cancer alone. The area under the curve for all adults did not change substantially by gender or by increasing the minimum age of testing. Using ≥10 µg Hb/g faeces, 10% of adults would be investigated to detect 91% of cancers, a number needed to scope of ten to detect one cancer. Using ≥7, ≥50 and ≥150 µg Hb/g faeces, 11%, 4% and 3% of adults would be investigated, and 91%, 74% and 54% cancers detected, respectively. CONCLUSION: A FIT threshold of ≥10 µg Hb/g faeces would be appropriate to triage adult patients presenting to primary care with symptoms of serious colorectal disease. FIT may be used to reprioritise patients referred with colorectal cancer symptoms whose investigations have been delayed by the COVID-19 pandemic.

The association between unexpected weight loss and cancer diagnosis in primary care: a matched cohort analysis of 65,000 presentations.

BACKGROUND: We aimed to understand the time period of cancer diagnosis and the cancer types detected in primary care patients with unexpected weight loss (UWL) to inform cancer guidelines. METHODS: This retrospective matched cohort study used cancer registry linked electronic health records from the UK's Clinical Practice Research Datalink from between 2000 and 2014. Univariable and multivariable time-to-event analyses examined the association between UWL, and all cancers combined, cancer site and stage. RESULTS: In all, 63,973 patients had UWL recorded, of whom 1375 (2.2%) were diagnosed with cancer within 2 years (days-to-diagnosis: mean 181; median 80). Men with UWL (HR 3.28 (2.88-3.73)) and women (1.87 (1.68-2.08)) were more likely than comparators to be diagnosed with cancer within 3 months. The association was greatest in men aged ≥50 years and women ≥70 years. The commonest cancers were pancreas, cancer of unknown primary, gastro-oesophageal, lymphoma, hepatobiliary, lung, bowel and renal-tract. The majority were late-stage, but there was some evidence of association with stage II and stage III cancers. In the 3-24 months after presenting with UWL, cancer diagnosis was less likely than in comparators. CONCLUSION: UWL recorded in primary care is associated with a broad range of cancer sites of early and late-stage.